This proposal is for a Program Project Grant consisting of four Projects and three Cores. Its overall goal is to investigate interactions betwee spinal circuits and the musculoskeletal system to promote more effective movement-related rehabilitation evaluation and therapeutic strategies. In each of the Projects this objective will b studied in model systems. In Project I (English), the effects of modifying the dosing, pattern, and therapeutic window of treatment with modest daily exercise in the form of treadmill training as a treatment for peripheral nerve injuries will be investigated. In Project II (Prilutsky/Gregor), the role of proprioceptive feedback in shaping functionally appropriate compensations to paralysis of selected muscles and the potential for therapeutic interventions that differentially affect lengh and force dependent feedback from, and mechanical demands on, reinnervated muscles will be studied. In Project III (Nichols), the measurement of limb mechanics will be used to evaluate changes in spinal circuitry resulting from perturbations of musculoskeletal circuits. In Project IV (Wolpaw/Chen), the role of descending neural systems in regulating the interactions of spinal and musculoskeletal circuits will be evaluated. The Projects are supported by Administrative and Technical Cores and a Clinician Scientist Advisory Board. One role of the latter is the implementation of a novel form of two way communication between Project scientists and rehabilitation clinicians. This PPG brings together a team of established scientists from diverse backgrounds, with a common goal to continue to strengthen the science base underlying clinical rehabilitation.